The unifying theme of this research program is to find innovative solutions to complex problems in total synthesis using oxidative methods for C-C bond formation. Synthetic tools to forge dissonant functional group relationships in a direct and efficient fashion are sorely lacking in the synthetic chemist's "tool box". When the broad range of natural products that are amenable to dissonant bond disconnections is considered, the development of new methods to form such bonds is a highly attractive area of research in organic chemistry. While our lab has registered several successes in the arena of oxidative coupling, it is abundantly clear that very little is actually known about the process. Our main goal is to gain insight into the requirements necessary for selective heterocouplings of carbonyl enolates, thus seeking to fill a gap in synthetic chemistry. There are remarkable advantages to be gained in terms of efficiency (lack of protecting groups, halogens, disposable functional groups), practicality (extremely concise sequences), stereocontrol (complete diastereoselectivity often observed), and conservation of oxidation state (oxidation state increases linearly in a synthesis by using innate functionality) when oxidative C -C bond formation is employed strategically. In the total synthesis realm, the following will be accomplished using oxidative C-C bond formation: (1) total synthesis of several challenging members of the hapalindole and ambiguine family, (2) total synthesis of the structurally captivating and highly bioactive welwitindolinones, and (3) synthesis of simplified analogs of the stephacidins and determination of their mechanism of action in collaboration with Prof. Benjamin Cravatt. These projects will also serve as an excellent training ground for students who intend to enter the field of drug discovery. In collaboration with the NCI and Professors Robert Abraham, William Fenical, and Ben Cravatt the biological evaluation of the stephacidins, hapalindoles, fischerindoles, welwitindolinones, and ambiguines will be undertaken in earnest, with the goal of studying, and perhaps even enhancing their biological activity.